U.S. FDA Approves IBRANCE for the Treatment of Men with HR+, HER2- Metastatic Breast Cancer

April 4, 2019 Off By BusinessWire

Approval of expanded indication based predominately on real-world data

NEW YORK–(BUSINESS WIRE)–Pfizer (NYSE:PFE) today announced that the U.S. Food and Drug
Administration (FDA) approved a supplemental New Drug Application (sNDA)
to expand the indications for IBRANCE^® (palbociclib) in
combination with an aromatase inhibitor or fulvestrant to include men
with hormone receptor-positive (HR+), human epidermal growth factor
receptor 2-negative (HER2-) advanced or metastatic breast cancer. The
approval is based on data from electronic health records and
postmarketing reports of the real-world use of IBRANCE in male patients
sourced from three databases: IQVIA Insurance database, Flatiron Health
Breast Cancer database and the Pfizer global safety database.

“With this approval, we are now able to offer IBRANCE to the underserved
male breast cancer community and provide more patients with HR+, HER2-
metastatic breast cancer the opportunity to access an innovative
medicine,” said Chris Boshoff, M.D., Ph.D., Chief Development Officer,
Oncology, Pfizer Global Product Development. “We appreciate that our
partnership with the FDA has allowed us to take a significant step
forward in the use of real-world data to bring medicines to patients who
are most in need.”

IBRANCE is now approved for adult patients with HR+, HER2- advanced or
metastatic breast cancer in combination with an aromatase inhibitor as
initial endocrine based therapy in postmenopausal women or in men; or
with fulvestrant in patients with disease progression following
endocrine therapy. With today’s approval, IBRANCE is the first and only
CDK 4/6 inhibitor indicated in combination with an aromatase inhibitor
for the first-line treatment of men with HR+, HER2- metastatic breast
cancer in the U.S.

“Men with breast cancer have limited treatment options, making access to
medicines such as IBRANCE critically important,” said Bret Miller,
founder of the Male Breast Cancer Coalition. “We applaud the use of
real-world data, a new approach to drug review, to make IBRANCE
available to certain men with metastatic breast cancer and help address
an unmet need for these patients.”

Real-world data is playing an increasingly important role in expanding
the use of already approved innovative medicines.¹ Due to the
rarity of breast cancer in males, fewer clinical trials are conducted
that include men resulting in fewer approved treatment options. In the
U.S. in 2019, it is estimated that there will be 2,670 new cases of
invasive breast cancer and about 500 deaths from metastatic breast
cancer in males.² The 21st Century Cures Act, enacted in
2016, was created to help accelerate medical product development,
allowing new innovations and advances to become available to patients
who need them faster and more efficiently.³ This law places
additional focus on the use of real-world data to support regulatory
decision-making.⁴

Detailed analysis of the use of IBRANCE in men with HR+, HER2- advanced
or metastatic breast cancer will be presented at an upcoming medical
meeting. Based on limited data from postmarketing reports and electronic
health records, the safety profile for men treated with IBRANCE is
consistent with the safety profile in women treated with IBRANCE.⁵

About IBRANCE^® (palbociclib) 125 mg capsules

IBRANCE is an oral inhibitor of CDKs 4 and 6,⁶ which are key
regulators of the cell cycle that trigger cellular progression.^7,8
In the U.S., IBRANCE is indicated for the treatment of adult patients
with hormone receptor-positive (HR+), human epidermal growth factor
receptor 2-negative (HER2-) advanced or metastatic breast cancer in
combination with an aromatase inhibitor as initial endocrine based
therapy in postmenopausal women or in men; or with fulvestrant in
patients with disease progression following endocrine therapy.

IBRANCE currently is approved in more than 90 countries and has been
prescribed to more than 200,000 patients globally.

The full prescribing information for IBRANCE can be found here.

IMPORTANT IBRANCE^®(palbociclib) SAFETY
INFORMATION FROM THE U.S. PRESCRIBING INFORMATION

Neutropenia was the most frequently reported adverse reaction in
PALOMA-2 (80%) and PALOMA-3 (83%). In PALOMA-2, Grade 3 (56%) or 4 (10%)
decreased neutrophil counts were reported in patients receiving IBRANCE
plus letrozole. In PALOMA-3, Grade 3 (55%) or Grade 4 (11%) decreased
neutrophil counts were reported in patients receiving IBRANCE plus
fulvestrant. Febrile neutropenia has been reported in 1.8% of patients
exposed to IBRANCE across PALOMA-2 and PALOMA-3. One death due to
neutropenic sepsis was observed in PALOMA-3. Inform patients to promptly
report any fever.

Monitor complete blood count prior to starting IBRANCE, at the beginning
of each cycle, on Day 15 of first 2 cycles and as clinically indicated.
Dose interruption, dose reduction, or delay in starting treatment cycles
is recommended for patients who develop Grade 3 or 4 neutropenia.

Based on the mechanism of action, IBRANCE can cause fetal harm.
Advise females of reproductive potential to use effective contraception
during IBRANCE treatment and for at least 3 weeks after the last dose.
IBRANCE may impair fertility in males and has the potential to
cause genotoxicity. Advise male patients to consider sperm preservation
before taking IBRANCE. Advise male patients with female partners of
reproductive potential to use effective contraception during IBRANCE
treatment and for 3 months after the last dose. Advise females to inform
their healthcare provider of a known or suspected pregnancy. Advise
women not to breastfeed during IBRANCE treatment and for 3 weeks
after the last dose because of the potential for serious adverse
reactions in nursing infants.

The most common adverse reactions (≥10%) of any grade
reported in PALOMA-2 for IBRANCE plus letrozole vs placebo plus
letrozole were neutropenia (80% vs 6%), infections (60% vs 42%),
leukopenia (39% vs 2%), fatigue (37% vs 28%), nausea (35% vs 26%),
alopecia (33% vs 16%), stomatitis (30% vs 14%), diarrhea (26% vs 19%),
anemia (24% vs 9%), rash (18% vs 12%), asthenia (17% vs 12%),
thrombocytopenia (16% vs 1%), vomiting (16% vs 17%), decreased appetite
(15% vs 9%), dry skin (12% vs 6%), pyrexia (12% vs 9%), and dysgeusia
(10% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-2
for IBRANCE plus letrozole vs placebo plus letrozole were neutropenia
(66% vs 2%), leukopenia (25% vs 0%), infections (7% vs 3%), and anemia
(5% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-2 for
IBRANCE plus letrozole vs placebo plus letrozole were decreased WBC (97%
vs 25%), decreased neutrophils (95% vs 20%), anemia (78% vs 42%),
decreased platelets (63% vs 14%), increased aspartate aminotransferase
(52% vs 34%), and increased alanine aminotransferase (43% vs 30%).

The most common adverse reactions (≥10%) of any grade reported in PALOMA-3
for IBRANCE plus fulvestrant vs placebo plus fulvestrant were
neutropenia (83% vs 4%), leukopenia (53% vs 5%), infections (47% vs
31%), fatigue (41% vs 29%), nausea (34% vs 28%), anemia (30% vs 13%),
stomatitis (28% vs 13%), diarrhea (24% vs 19%), thrombocytopenia (23% vs
0%), vomiting (19% vs 15%), alopecia (18% vs 6%), rash (17% vs 6%),
decreased appetite (16% vs 8%), and pyrexia (13% vs 5%).

The most frequently reported Grade ≥3 adverse reactions (≥5%) in PALOMA-3
for IBRANCE plus fulvestrant vs placebo plus fulvestrant were
neutropenia (66% vs 1%) and leukopenia (31% vs 2%).

Lab abnormalities of any grade occurring in PALOMA-3 for
IBRANCE plus fulvestrant vs placebo plus fulvestrant were decreased WBC
(99% vs 26%), decreased neutrophils (96% vs 14%), anemia (78% vs 40%),
decreased platelets (62% vs 10%), increased aspartate aminotransferase
(43% vs 48%), and increased alanine aminotransferase (36% vs 34%).

Avoid concurrent use of strong CYP3A inhibitors. If patients must
be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75
mg. If the strong inhibitor is discontinued, increase the IBRANCE dose
(after 3-5 half-lives of the inhibitor) to the dose used prior to the
initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice
may increase plasma concentrations of IBRANCE and should be avoided.
Avoid concomitant use of strong CYP3A inducers. The dose of sensitive
CYP3A substrates with a narrow therapeutic index may need to be
reduced as IBRANCE may increase their exposure.

For patients with severe hepatic impairment (Child-Pugh class C),
the recommended dose of IBRANCE is 75 mg. The pharmacokinetics of
IBRANCE have not been studied in patients requiring
hemodialysis.

About Pfizer Oncology

At Pfizer Oncology, we are committed to advancing medicines wherever we
believe we can make a meaningful difference on the lives of patients.
Today, Pfizer Oncology has an industry-leading portfolio of 18 approved
innovative cancer medicines and biosimilars across more than 20
indications, including breast, prostate, kidney, lung and hematology.
Pfizer Oncology is striving to change the trajectory of cancer.

Working together for a healthier world^®

At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world’s
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world’s
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all who
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In addition, to learn more, please visit us on www.pfizer.com
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and @Pfizer_News,
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DISCLOSURE NOTICE: The information contained in this release is as of
April 4, 2019. Pfizer assumes no obligation to update forward-looking
statements contained in this release as the result of new information or
future events or developments.

This release contains forward-looking information about the expansion
of the indication for IBRANCE (palbociclib) in combination with an
aromatase inhibitor or fulvestrant to include men with hormone
receptor-positive (HR+), human epidermal growth factor receptor
2-negative (HER2-) advanced or metastatic breast cancer and Pfizer
Oncology, including their potential benefits, that involves substantial
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such statements. Risks and
uncertainties include, among other things, uncertainties regarding the
commercial success of IBRANCE; the uncertainties inherent in research
and development, including the ability to meet anticipated clinical
endpoints, commencement and/or completion dates for our clinical trials,
regulatory submission dates, regulatory approval dates and/or launch
dates, as well as the possibility of unfavorable new clinical data and
further analyses of existing clinical data; the risk that clinical trial
data are subject to differing interpretations and assessments by
regulatory authorities; whether regulatory authorities will be satisfied
with the design of and results from our clinical studies; whether and
when any drug applications may be filed in any other jurisdictions for
IBRANCE, for any additional indications for IBRANCE or for any other
oncology products; whether and when any such applications may be
approved by regulatory authorities, which will depend on myriad factors,
including making a determination as to whether the product’s benefits
outweigh its known risks and determination of the product’s efficacy,
and, if approved, whether IBRANCE or any such other oncology products
will be commercially successful; decisions by regulatory authorities
impacting labeling, safety, manufacturing processes and/or other matters
that could affect the availability or commercial potential of IBRANCE or
any other oncology products; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2018 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results,” as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at www.sec.gov
and www.pfizer.com.

_______________________________
¹ FDA: Real World
Evidence. https://www.fda.gov/scienceresearch/specialtopics/realworldevidence/default.htm.
Accessed March 5, 2019.
² American Cancer Society. Key
statistics for breast cancer in men. https://www.cancer.org/cancer/breast-cancer-in-men/about/key-statistics.html.
Accessed March 20, 2019.
³ FDA: 21st Century Cures Act. https://www.fda.gov/regulatoryinformation/lawsenforcedbyfda/significantamendmentstothefdcact/21stcenturycuresact/default.htm.
Accessed March 5, 2019.
⁴ FDA: Real World Evidence. https://www.fda.gov/ScienceResearch/SpecialTopics/RealWorldEvidence/default.htm.
Accessed March 5, 2019.
⁵ Pfizer global safety database.
⁶
IBRANCE^® (palbociclib) Prescribing Information. New York. NY:
Pfizer Inc: 2019.
⁷ Weinberg, RA. pRb and Control of the
Cell Cycle Clock. In: Weinberg RA, ed. The Biology of Cancer. 2nd ed.
New York, NY: Garland Science; 2014:275-329.
⁸ Sotillo
E, Grana X. Escape from Cellular Quiescence. In: Enders GH, ed. Cell
Cycle Deregulation in Cancer. New York, NY: Humana Press; 2010:3-22.